This phase I trial studies the side effects and the safety of injecting HSV1716 (a new experimental therapy) into or near the tumor resection cavity. The injection will be done at the time of surgery. HSV1716 is a virus that has a gene which has been changed or removed (mutated) in such a way that lets the virus multiply in dividing cells of the tumor and kills the tumor cells.

Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:

MTD of oncolytic HSV-1716, defined as the highest dose level at which 0 out of 3 or at most one out of 6 patients have been treated experiencing a dose limiting toxicity and the next higher dose level has been determined to be too toxic [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]

Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

Secondary Outcome Measures:

Antiviral immune responses [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]

Summarized and reported descriptively.

Systemic viremia and viral shedding [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]

Summarized and reported descriptively.

Progression free survival [ Time Frame: From the date of initial protocol treatment to the earliest date of disease progression, second malignancy or death for patients who fail; and to the date of last contact for patients who remain at risk for failure, assessed up to 15 years ] [ Designated as safety issue: No ]

Overall survival [ Time Frame: From the date of initial protocol treatment to the date of death for patients who fail; and to the date of last contact for patients who remain at risk for failure, assessed up to 15 years ] [ Designated as safety issue: No ]

After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 4 years, and then annually for 10 years.

Eligibility

Ages Eligible for Study:

12 Years to 21 Years (Child, Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Imaging evaluations necessary to establish eligibility for study entry must be done within three (3) weeks prior to registration; all other evaluations necessary to establish eligibility for study entry must be done within two (2) weeks prior to registration; in the event that the patient's condition deteriorates (performance score < 60) within 48 hours prior to the injection the patient is no longer eligible to receive HSV1716 injection

Patients must have a histologically-confirmed primary diagnosis of high-grade glioma (HGG) (such as glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma, anaplastic ganglioglioma, high grade astrocytoma, not otherwise specified [NOS]) that is recurrent or refractory to conventional therapy; patients with metastatic disease are not eligible

Patients must be those for whom surgical resection is clinically indicated; the intent of surgical resection may include debulking or attempt to resect as much of the tumor as safely feasible; if a gross total or near total resection is not feasible, HSV1716 injection into the wall of the resection cavity, encompassing residual tumor, is permissible

Patients must be amenable to receiving 1 dose of HSV1716 intra-operatively with planned HSV1716 injection sites >= 1 cm from the ventricular system AND meet at least one of the criteria below based upon pre-surgical magnetic resonance imaging (MRI):

Tumor is >= 1 cm from the ventricular system

Patients whose tumors that are =< 1 cm from the ventricular system are eligible if there is sufficient space within the tumor cavity and/or residual tumor to perform the HSV 1716 injections that are >= 1 cm from the ventricular system

An intraoperative MRI upon resection will confirm the distance of the planned injection sites from the ventricular system prior to the HSV1716 injection; intra-operatively, the neurosurgeon may decide to not inject the HSV1716 or may revise the sites of HSV1716 injection if injection cannot be guaranteed >= 1 cm from the ventricular system; patient will removed from the study if there are not sufficient areas in the tumor cavity to guarantee injection of HSV1716 >= 1 cm from the ventricular system

Patients must have received prior therapy other than surgery and must have fully recovered from the acute treatment related toxicities of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three (3) weeks prior to study registration treatment or at least six (6) weeks if nitrosourea

Investigational/Biologic agent:

Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent >= 7 days prior to study registration

For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur

Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration; Note: A list of the half-lives of commonly used monoclonal antibodies is available on the Pediatric Brain Tumor Consortium (PBTC) webpage under Generic Forms and Templates

Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration; this is to be documented at baseline

Patients with central nervous system (CNS) tumors who are receiving dexamethasone must have been on a stable or decreasing dose of dexamethasone for the 7 days prior to enrollment

Growth factors that support platelet or white cell number or function must not have been administered within the past 7 days; growth factors include: GCSF (filgrastim), PEG-GCSF (Neulasta), GM-CSF (sargramostim) and erythropoietin

Documented evidence of negative tests for the presence of hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)1/2 antibodies within the three months preceding study entry; subjects who do not have such evidence must undergo appropriate testing prior to virus administration; HIV-positive patients on combination antiretroviral therapy are ineligible

Female patients of childbearing potential must have a negative serum or urine pregnancy test at the time of enrollment

Ability to understand and the willingness to sign a written informed consent document according to institutional guidelines

Patients who are currently receiving other anti-cancer agents are excluded from this trial

Patients with history of prior HSV encephalitis or encephalitis due to other etiologies

There is no available information regarding human fetal or teratogenic toxicities

Pregnant women are excluded to avoid the risk of systemic intrauterine/neonatal HSV infection

Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method from the time of study entry to a period of no less than four months post the HSV1716 injection

Women who participate in this study must agree not to breastfeed from study entry to a period of no less than four months post the HSV1716 injection

Subjects whose primary physicians determine that anti-HSV antiviral therapy (such as acyclovir, ganciclovir, foscarnet, etc.) cannot be safely discontinued from 2 days prior to the injection to 28 days following the injection are excluded from this study

Patients on systemic anticoagulants are excluded from this study

Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02031965